Dental Biochemistry 1- (6)

Carbohydrates Metabolism Part I

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Glucose metabolism

Importance of Glucose: 1. Glucose is the preferred source of energy for most

of the body tissues. Brain cells derive energy mainly from glucose.

2. When glucose metabolism is deranged, life-threatening conditions may occur. A minimum amount of glucose is always required for normal functioning.

3. Normal fasting plasma glucose level is 70 to 110 mg/dl. After a heavy carbohydrate meal, in a normal person, this level is below 150 mg/dl.

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Glucose is used in • Oxidation: The pathways for oxidation of glucose are classified into two main groups:

A. The major pathways which are mainly for energy production:

1. Glycolysis.

2. Citric acid cycle (CAC).

B. The minor pathways for oxidation which are not for energy production:

1. Hexose monophosphate shunt (HMS).

2. Uronic acid pathway.

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• II. Conversion to biologically active substances as:

1. Galactose: which is essential for formation of lactose, glycolipids, mucopolysaccharides, ...etc.

2. Fructose: needed for nutrition of sperms.

3. Amino sugars.

4. Non-essential amino acids.

5. Fatty acids.

6. Ribose-5-P.

7. Glucuronic acid.

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• III. Storage of glucose:

1. As glycogen in the liver and muscles mainly.

2. As triglycerides (TG), mainly in adipose tissues.

• IV. Excretion of glucose in urine:

When blood glucose level exceeds a certain limit (renal sugar threshold), it will pass to urine. This will occur when blood glucose level is above 180 mg/dl and this is known as glucosuria.

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Glycolysis (Embden-Meyerhof Pathway)

Importance of the pathway • In this pathway glucose is converted to pyruvate

(aerobic condition) or lactate (anaeroboic condition), along with production of a small quantity of energy.

• All the reaction steps take place in the cytoplasm. It is the only pathway that is taking place in all the cells of the body.

• Glycolysis is the only source of energy in erythrocytes. 6

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Importance of glycolysis

• I-Energy production :

• 1. Under aerobic conditions:

Glucose ------→ 2 Pyruvate + 8 ATP.

For tissues that have mitochondria, glycolysis is considered a preparatory step for complete oxidation via citric acid cycle since pyruvate is transported into the mitochondria to provide oxaloacetate or active acetate where it is oxidized by CAC for more energy.

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• The hydrogens of NADH produced by glycolysis are transported to the mitochondria mainly to be oxidized by electron transport chain (ETC).

• 2. Under anaerobic conditions:

Glucose ------→ 2 lactate + 2 ATP

Pyruvate is reduced to lactate in a reversible reaction catalyzed by lactate dehydrogenase (LDH).

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• This occurs in muscles during severe exercise (hypoxic conditions) and in tissues that lack mitochondria as RBCs and lens.

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Cori’s cycle or lactic acid cycle

• In an actively contracting muscle, only about 8% of the pyruvate is utilized by the citric acid cycle, and the remaining molecules are therefore reduced to lactate.

• The lactic acid thus, generated should not be allowed to accumulate in the muscle tissues.

• The muscle cramps, often associated with strenuous muscular exercise, are through to be due to lactate accumulation.

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• This lactate diffuses into the blood. During exercise, blood lactate level is increased appreciably.

• Lactate then reaches liver, where it is oxidized to pyruvate.

• It is then taken up through gluconeogenesis pathway, and becomes glucose which can enter into blood and then taken to muscle.

• This cycle is called Cori’s cycle, by which the Lactate is efficiently reutilized by the body.

• Carl Cori and Gerty Cori were awarded Nobel prize in 1947.

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glycolysisRegulation of Hormonal regulation of glycolysis:

• a) Glucagon : is secreted in hypoglycemia or in carbohydrate deficiency. It affects liver cells mainly as follows:

It acts as inhibitors for glycolytic key enzymes (glucokinase,PFK-1, pyruvate kinase).

• b) Insulin: It is secreted in hyperglycemia and after carbohydrates feeding, it causes:

Stimulation of glycolytic key enzymes.

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Enzyme regulation

• The key irreversible regulatory Enzymes are:

- Hexokinase (glucokinase),

- Phosphofructokinase (PFK-1)

- Pyruvate kinase.

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Inhibitors of glycolysis: 1- 2- deoxyglucose inhibits

hexokinase.

2- Mercury and iodoacetate inhibit

glyceraldehyde-3-P dehydrogenase.

3- Fluoride inhibits enolase by removal of Mg2+ as Mg fluoride.

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Pyruvate as a junction point Pyruvate occupies an important junction

between various metabolic pathways. It may be decarboxylated to acetyl-CoA which enters the TCA cycle, or may be utilized for fatty acid synthesis.

Pyruvate may be carboxylated to oxaloacetate which is used for gluconeogenesis.

Pyruvate dehydrogenase step is the committed step towards oxidation of glucose.

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Citric acid cycle (CAC)

or Tricarboxylic Acid Cycle (TCA)

or Krebs Cycle Definition:

It is a series of reactions in mitochondria, that

brings about the catabolism of acetyl residues,

liberating hydrogen equivalents which upon

oxidation, leads to the release of energy.

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Functions of the Citric Acid Cycle 1. It is the final common oxidation pathway that

oxidises acetyl CoA to CO2.

2. Energy production, every one mole of acetyl- CoA produces 12 moles of ATP.

3. It is the source of reduced coenzymes that provide the substrate for the respiratory chain.

4. It acts as a link between catabolic and anabolic pathway (amphibolic role).

5. It provides precursors for synthesis of amino acids and nucleotides.

6. Components of the cycle have direct or indirect controlling effects on key enzymes of other pathways.

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Total ATP produced from complete oxidation of

one molecule of glucose during glycolysis,

oxidative decarboxylation and CAC :

Glycolysis G → 2PA 8 ATP

Oxidative decarboxylation 2PA → 2 acetyl CoA 6 ATP

(2 NADH + H+ ×3)

Oxidation of 2 acetyl CoA in CAC → (12 ATP ×2) 24 ATP -------------------

38 ATP

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Inhibitors of CAC

1- Fluorocitrate inhibits aconitase.

2- Mercury and arsenite inhibit pyruvate and α–

ketoglutarate dehydrogenase complex.

3- Malonic acid inhibits succinic acid

dehydrogenase.

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Gluconeogenesis

• i. It is the process by which new glucose is synthesized from noncarbohydrate precursors like lactate, glycerol and glucogenic amino acids.

• ii. It occurs mainly in the liver.

• iii. Gluconeogenesis involves several enzymes of glycolysis, but it is not a reversal of glycolysis.

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